Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro genotoxicity (bacterial cells): Negative based on QSAR

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation.
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
OECD Toolbox v2.3
Toolbox prediction report is attached in IUCLID
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
without
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined

Estimation method: (Q)SAR prediction
In domain

Conclusions:
The prediction without metabolic activation was negative.
Executive summary:

The TIMES model for Ames mutagenicity was used within the OECD Toolbox v2.3. The prediction without metabolic activation was negative. Additional supporting documentation is provided in the attached prediction report.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation.
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
OECD Toolbox v2.3
Toolbox prediction report is attached in IUCLID
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined

Estimation method: (Q)SAR prediction
In domain

Conclusions:
The prediction with metabolic activation was negative.
Executive summary:

The TIMES model for Ames mutagenicity was used within the OECD Toolbox v2.3. The prediction with metabolic activation was negative. Additional supporting documentation is provided in the attached prediction report.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation.
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
OECD Toolbox v3
Toolbox prediction report is attached in IUCLID
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
without
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes maximal value from the 5 nearest neighbours

Conclusions:
Substances were subcategorised on the basis of common MOA. Data was taken for all strains without metabolic activation. The read-across prediction was negative.
Executive summary:

The OECD Toolbox v3 ws used to undertake an endpoint specific grouping for the Ames endpoint. Substances were subcategorised on the basis of common MOA. Data was taken for all strains without metabolic activation. The read-across prediction was negative. Additional supporting documentation is provided in the attached prediction report.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation.
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
OECD Toolbox v3
Toolbox prediction report is attached in IUCLID
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes maximal value from the 5 nearest neighbours

Conclusions:
Substances were subcategorised on the basis of common MOA. Data was taken for all strains with activation. The read-across prediction was negative.
Executive summary:

The OECD Toolbox v3 ws used to undertake an endpoint specific grouping for the Ames endpoint. Substances were subcategorised on the basis of common MOA. Data was taken for all strains with activation. The read-across prediction was negative. Additional supporting documentation is provided in the attached prediction report.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation.
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
OECD Toolbox v3
Toolbox prediction report is attached in IUCLID
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes maximal value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

("a" and ("b" and "c" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alcohol AND Carbohydrate/ Monosaccharide AND Dihydroxyl group AND Ether, cyclic AND Hemiacetal AND Saturated heterocyclic fragment AND Tetrahydropyran by Organic functional groups

Domain logical expression index: "b"

Parametric boundary:The target chemical should have a value of log Kow which is >= -7.37

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= -2.88

Conclusions:
Substances were subcategorised on the basis of common MOA. Data was taken for all strains with and without activation. The read-across prediction was negative.
Executive summary:

The OECD Toolbox v3 ws used to undertake an endpoint specific grouping for the Ames endpoint. Substances were subcategorised on the basis of common MOA. Data was taken for all strains with and without activation. The read-across prediction was negative. Additional supporting documentation is provided in the attached prediction report.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Data from a higher tier in vivo 2-year carcinogenicity study in rats was available.  No tumours were observed in this carcinogenicity assay, therefore the test substance is not a genotoxic mutagen or a carcinogen.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

The test substance was evaluated by a range of non-testing approach utilising both the grouping capabilities within the OECD Toolbox as well as TIMES, an expert system. A read-across prediction was derived on Ames data both with and without metabolic activation. A prediction was also derived based on overall Ames result outcomes. Finally, predictions were derived using TIMES with and without metabolic activation. On the basis of these 5 predictions, the results were consistent demonstrating that the test substance was negative for Ames. The absence of alerting groups for the test substance was effectively confirmed by the QSAR and read-across predictions derived.

Justification for classification or non-classification

The test substance is expected to be negative for genotoxicity in bacterial cells and did not produce tumours in a carcinogenicity study in rats. Therefore, no classification is required for genetic toxicity according to EU Directive 67/548/EEC and EU Classification and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.